O14493 (CLD4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Claudin-4

Alternative name(s):
Clostridium perfringens enterotoxin receptor
Short name=CPE-R
Short name=CPE-receptor
Williams-Beuren syndrome chromosomal region 8 protein

Gene names

Name:	CLDN4
Synonyms:	CPER, CPETR1, WBSCR8

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	209 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays a major role in tight junction-specific obliteration of the intercellular space By similarity.
Subunit structure	Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3. Interacts with EPHA2; phosphorylates CLDN4 and may regulate tight junctions. Ref.4
Subcellular location	Cell junction › tight junction By similarity. Cell membrane; Multi-pass membrane protein By similarity.
Post-translational modification	Phosphorylated. Phosphorylation by EPHA2 is stimulated by EFNA1 and alters interaction with TJP1. Ref.4
Involvement in disease	CLDN4 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.
Sequence similarities	Belongs to the claudin family.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Membrane Tight junction
Disease	Williams-Beuren syndrome
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	calcium-independent cell-cell adhesion Inferred from sequence or structural similarity. Source: UniProtKB female pregnancy Inferred from electronic annotation. Source: Ensembl response to progesterone Inferred from electronic annotation. Source: Ensembl signal transduction Traceable author statement Ref.1. Source: GOC
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: Ensembl apicolateral plasma membrane Inferred from electronic annotation. Source: Ensembl basal plasma membrane Inferred from electronic annotation. Source: Ensembl integral component of plasma membrane Traceable author statement Ref.1. Source: ProtInc lateral plasma membrane Inferred from electronic annotation. Source: Ensembl plasma membrane Traceable author statement Ref.1PubMed 9892664. Source: ProtInc tight junction Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	identical protein binding Inferred from sequence or structural similarity. Source: UniProtKB structural molecule activity Inferred from electronic annotation. Source: InterPro transmembrane signaling receptor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 209	209	Claudin-4		PRO_0000144743
Regions
	Topological domain	1 – 7	7	Cytoplasmic Potential
	Transmembrane	8 – 28	21	Helical; Potential
	Topological domain	29 – 81	53	Extracellular Potential
	Transmembrane	82 – 102	21	Helical; Potential
	Topological domain	103 – 117	15	Cytoplasmic Potential
	Transmembrane	118 – 138	21	Helical; Potential
	Topological domain	139 – 160	22	Extracellular Potential
	Transmembrane	161 – 181	21	Helical; Potential
	Topological domain	182 – 209	28	Cytoplasmic Potential
	Region	1 – 103	103	Interaction with EPHA2
	Region	208 – 209	2	Interactions with TJP1, TJP2 and TJP3 By similarity
Amino acid modifications
	Modified residue	208	1	Phosphotyrosine; by EPHA2 Ref.4
Experimental info
	Mutagenesis	208	1	Y → F: Loss of phosphorylation by EPHA2. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	O14493 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 0659A93AA5F0E4C5	FASTA	209	22,077
	10 20 30 40 50 60 MASMGLQVMG IALAVLGWLA VMLCCALPMW RVTAFIGSNI VTSQTIWEGL WMNCVVQSTG 70 80 90 100 110 120 QMQCKVYDSL LALPQDLQAA RALVIISIIV AALGVLLSVV GGKCTNCLED ESAKAKTMIV 130 140 150 160 170 180 AGVVFLLAGL MVIVPVSWTA HNIIQDFYNP LVASGQKREM GASLYVGWAA SGLLLLGGGL 190 200 LCCNCPPRTD KPYSAKYSAA RSAAASNYV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Clostridium perfringens enterotoxin utilizes two structurally related membrane proteins as functional receptors in vivo." Katahira J., Sugiyama H., Inoue N., Horiguchi Y., Matsuda M., Sugimoto N. J. Biol. Chem. 272:26652-26658(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal brain.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon.
[4]	"EphA2 phosphorylates the cytoplasmic tail of Claudin-4 and mediates paracellular permeability." Tanaka M., Kamata R., Sakai R. J. Biol. Chem. 280:42375-42382(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EPHA2 AND TJP1, MUTAGENESIS OF TYR-208, PHOSPHORYLATION AT TYR-208 BY EPHA2.
[5]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB000712 mRNA. Translation: BAA22984.1. BT006989 mRNA. Translation: AAP35635.1. BC000671 mRNA. Translation: AAH00671.1.
RefSeq	NP_001296.1. NM_001305.4.
UniGene	Hs.647036. Hs.729359.
3D structure databases
ProteinModelPortal	O14493.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
BioGrid	107756. 2 interactions.
STRING	9606.ENSP00000342445.
Protein family/group databases
TCDB	1.H.1.1.6. the claudin tight junction (claudin) family.
PTM databases
PhosphoSite	O14493.
Proteomic databases
PaxDb	O14493.
PRIDE	O14493.
Protocols and materials databases
DNASU	1364.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000340958; ENSP00000342445; ENSG00000189143. ENST00000431918; ENSP00000388639; ENSG00000189143. ENST00000435050; ENSP00000409544; ENSG00000189143. ENST00000573160; ENSP00000461070; ENSG00000262988. ENST00000573932; ENSP00000460384; ENSG00000262988. ENST00000574332; ENSP00000461587; ENSG00000262988.
GeneID	1364.
KEGG	hsa:1364.
UCSC	uc003tzi.4. human.
Organism-specific databases
CTD	1364.
GeneCards	GC07P073213.
HGNC	HGNC:2046. CLDN4.
HPA	CAB002610. HPA007322.
MIM	602909. gene.
neXtProt	NX_O14493.
PharmGKB	PA26572.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG46413.
HOGENOM	HOG000220937.
HOVERGEN	HBG000643.
InParanoid	O14493.
KO	K06087.
OMA	TAHNVIR.
OrthoDB	EOG79KPGQ.
PhylomeDB	O14493.
TreeFam	TF331936.
Enzyme and pathway databases
Reactome	REACT_111155. Cell-Cell communication.
Gene expression databases
ArrayExpress	O14493.
Bgee	O14493.
CleanEx	HS_CLDN4.
Genevestigator	O14493.
Family and domain databases
InterPro	IPR006187. Claudin. IPR003550. Claudin4. IPR017974. Claudin_CS. IPR004031. PMP22/EMP/MP20/Claudin. [Graphical view]
PANTHER	PTHR12002. PTHR12002. 1 hit.
Pfam	PF00822. PMP22_Claudin. 1 hit. [Graphical view]
PRINTS	PR01077. CLAUDIN. PR01379. CLAUDIN4.
PROSITE	PS01346. CLAUDIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CLDN4. human.
GeneWiki	CLDN4.
GenomeRNAi	1364.
NextBio	5527.
PRO	O14493.
SOURCE	Search...

Entry information

Entry name

CLD4_HUMAN

Accession

Primary (citable) accession number: O14493

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	January 1, 1998
Last modified:	April 16, 2014
This is version 120 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.